Hydroxyurea + EPO for Sickle Cell Disease

(ACHiEvE-SCD Trial)

No longer recruiting at 1 trial location

Overseen By Jude C Jonassaint, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Julia Xu

Must be taking: Hydroxyurea

Must not be taking: Voxelotor, EPO

Disqualifiers: Chronic transfusion, Iron deficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of hydroxyurea and erythropoietin (EPO) to determine their effectiveness in treating chronic anemia in people with sickle cell disease (SCD). Researchers aim to assess the safety of this combination and its ability to boost hemoglobin levels, which are crucial for oxygen transport in the blood. Participants must be adults with a confirmed SCD diagnosis who have maintained a stable dose of hydroxyurea for at least 60 days. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

If you're taking hydroxyurea, L-glutamine, or crizanlizumab, you can continue these medications at the same dose and schedule during the study. However, you should not have taken voxelotor or EPO within 30 days before starting the study drug.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using erythropoietin (EPO) with hydroxyurea to treat sickle cell disease (SCD) could be safe. In one study, most patients who received this treatment showed improved hemoglobin levels, suggesting effectiveness without major issues.

Some evidence indicates that combining EPO with hydroxyurea helps manage the disease more effectively. This combination might allow for higher doses of hydroxyurea, which could benefit those at higher risk.

However, EPO has its drawbacks. It can sometimes cause problems like blood clots, especially in patients with a history of such issues. Overall, the treatment appears manageable for most patients, particularly with careful monitoring. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using erythropoietin (EPO) with hydroxyurea for sickle cell disease because it offers a novel approach to managing the condition. While standard treatments like hydroxyurea alone or blood transfusions help manage symptoms and prevent complications, adding EPO aims to boost hemoglobin levels more effectively. EPO works by stimulating the production of red blood cells, which could potentially improve oxygen delivery in the body and alleviate anemia more efficiently than current options. This combination treatment might offer a better solution for patients who don't respond well to existing therapies.

What evidence suggests that this trial's treatments could be effective for sickle cell disease?

Research has shown that erythropoietin (EPO) combined with hydroxyurea can help treat anemia in people with sickle cell disease (SCD). In this trial, participants on a stable dose of hydroxyurea will receive increasing doses of EPO. One study found that 87.5% of patients experienced an increase in hemoglobin levels by at least 1.0 g/dL after 12 weeks, suggesting this combination can effectively improve anemia. EPO also benefits those with kidney problems who cannot take high doses of hydroxyurea. Overall, this combination appears promising for managing long-term anemia in SCD. ^{1 2 3 4 6}

Who Is on the Research Team?

Julia Z Xu, MD, MScGH

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

Adults over 18 with confirmed sickle cell disease (HbSS or HbS/β0-thalassemia), not on blood transfusion programs, and without recent use of certain drugs like voxelotor or EPO. Participants must have been on a stable dose of hydroxyurea for at least 60 days and plan to continue it during the trial.

Inclusion Criteria

Screening transferrin saturation ≥ 20% and ferritin ≥ 100 ng/mL

Screening Hb ≤ 9.0 g/dL

I have been on a consistent dose of hydroxyurea for the last 60 days and plan to continue.

Exclusion Criteria

I have had very high blood pressure on two separate tests.

I have had a blood clot in the last 6 months.

I have not had a serious illness, infection, or pain crisis in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants on stable hydroxyurea therapy receive increasing doses of subcutaneous erythropoietin (EPO) for 12 weeks to assess safety and efficacy.

12 weeks

Regular visits for monitoring and dose adjustments

Extended Treatment

Participants may continue EPO treatment for an additional 12 weeks as clinically indicated, with further assessment of endpoints.

12 weeks

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Epoetin Alfa
• Hydroxyurea

Trial Overview The study is testing the combination of erythropoietin (EPO) with hydroxyurea to treat chronic anemia in sickle cell disease patients. It's a Phase 1/2 trial, meaning they're looking at safety and how well it works across multiple centers.

How Is the Trial Designed?

Group I: Erythropoietin Experimental Treatment 2 Interventions

Subjects on a stable dose of hydroxyurea will be treated with increasing doses of subcutaneous erythropoietin (EPO) as tolerated for an initial 12 weeks, during which the main safety and efficacy endpoints (including the primary endpoint of hemoglobin response) will be assessed. Subjects may continue on treatment for an additional 12 weeks as clinically indicated, with assessment of additional endpoints at the end of the 24-week study period.

Hydroxyurea is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Hydroxyurea for:

• Sickle cell disease
• Chronic myeloid leukemia
• Solid tumors
• Thrombocythemia

Approved in European Union as Hydroxycarbamide for:

• Sickle cell syndrome
• Chronic myeloid leukaemia
• Essential thrombocythaemia
• Polycythaemia vera

Approved in Canada as Hydroxyurea for:

• Sickle cell disease
• Chronic myeloid leukemia
• Thrombocythemia

Who Is Running the Clinical Trial?

Julia Xu

Lead Sponsor

Trials

1

Recruited

20+

Carnegie Mellon University

Collaborator

Trials

80

Recruited

540,000+

American Society of Hematology

Collaborator

Trials

14

Recruited

20,800+

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/178/530726/A-Phase-1b-2-Study-of-the-Efficacy-and-Safety-of

A Phase 1b/2 Study of the Efficacy and Safety of Combination ... This study aims to assess the efficacy and safety of using a standardized dosing regimen of EPO to treat anemia in patients with SCD stabilized on hydroxyurea.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3522485/

Combination Erythropoietin-Hydroxyurea Therapy in Sickle ... We conclude that EPO therapy may be useful in patients with SCD and renal insufficiency who are not tolerating, or likely to tolerate, HU at 15 mg/Kg.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124029252

A Phase 1b/2 Study of the Efficacy and Safety ... This study aims to assess the efficacy and safety of using a standardized dosing regimen of EPO to treat anemia in patients with SCD stabilized on hydroxyurea.

4. docwirenews.com docwirenews.com/post/preliminary-data-presented-on-epoetin-alfa-dose-escalation-with-stable-hydroxyurea-for-scd-anemia

Preliminary Data Presented on Epoetin Alfa Dose ... By week 12 of treatment, among the eight patients who completed the study regimen, 87.5% had a hemoglobin response of 1.0 g/dL or greater and a ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10923353/

Maximizing longevity: erythropoietin's impact on sickle cell ... The primary outcome measures include the change in haemoglobin levels, frequency of vaso-occlusive crises, and the need for blood transfusions.

6. mayoclinic.org mayoclinic.org/drugs-supplements/epoetin-alfa-injection-route/description/drg-20068065

Epoetin alfa (injection route) - Side effects & dosage Sickle cell anemia—Epoetin may not work properly. Blood clots (history of) or other problems with the blood or; Cancer, active or; Congestive ...